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Cytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins

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cris.lastimport.scopus2024-02-12T19:42:06Z
dc.abstract.enMitochondria are organelles with their own genomes, but they rely on the import of nuclear-encoded proteins that are translated by cytosolic ribosomes. Therefore, it is important to understand whether failures in the mitochondrial uptake of these nuclear-encoded proteins can cause proteotoxic stress and identify response mechanisms that may counteract it. Here, we report that upon impairments in mitochondrial protein import, high-risk precursor and immature forms of mitochondrial proteins form aberrant deposits in the cytosol. These deposits then cause further cytosolic accumulation and consequently aggregation of other mitochondrial proteins and disease-related proteins, including α-synuclein and amyloid β. This aggregation triggers a cytosolic protein homeostasis imbalance that is accompanied by specific molecular chaperone responses at both the transcriptomic and protein levels. Altogether, our results provide evidence that mitochondrial dysfunction, specifically protein import defects, contributes to impairments in protein homeostasis, thus revealing a possible molecular mechanism by which mitochondria are involved in neurodegenerative diseases.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorGoral, Tomasz
dc.contributor.authorPerni, Michele
dc.contributor.authorTurek, Michał
dc.contributor.authorKundra, Rishika
dc.contributor.authorStroobants, Karen
dc.contributor.authorChacinska, Agnieszka
dc.contributor.authorSladowska, Maria
dc.contributor.authorNowicka, Urszula
dc.contributor.authorDobson, Christopher M
dc.contributor.authorChroscicki, Piotr
dc.contributor.authorVendruscolo, Michele
dc.contributor.authorUszczyńska-Ratajczak, Barbara
dc.date.accessioned2024-01-24T21:15:29Z
dc.date.available2024-01-24T21:15:29Z
dc.date.issued2021
dc.description.accesstimeAT_PUBLICATION
dc.description.financePublikacja bezkosztowa
dc.description.versionFINAL_PUBLISHED
dc.description.volume10
dc.identifier.doi10.7554/ELIFE.65484
dc.identifier.issn2050-084X
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/104098
dc.identifier.weblinkhttps://cdn.elifesciences.org/articles/65484/elife-65484-v1.pdf
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofeLife
dc.rightsCC-BY-ND
dc.sciencecloudnosend
dc.subject.enC. elegans
dc.subject.enS. cerevisiae
dc.subject.enaggregation
dc.subject.enbiochemistry
dc.subject.enchaperones
dc.subject.enchemical biology
dc.subject.enhomeostasis
dc.subject.enmetastable proteins
dc.subject.enmitochondria
dc.subject.enneurodegeneration
dc.titleCytosolic aggregation of mitochondrial proteins disrupts cellular homeostasis by stimulating the aggregation of other proteins
dc.typeJournalArticle
dspace.entity.typePublication